Successful control measures to treat the transmission of Candida auris in Northern Italian Hospital.

Candida auris has emerged globally as a multidrug-resistant health care-associated fungal pathogen. In the literature, nosocomial outbreaks are reported worldwide. In addition, C. auris diffusion occurs in high-dependency settings with infections typically affecting critically ill patients, resulting in life-threatening disease. We describe the first documented case of C. auris in northeastern Italy and the measures applied to contain the transmission that led to zero collateral infections.

The organizational domain in HTA reports: towards a technology-oriented assessment.

BACKGROUND: Organizational aspects in Health Technology Assessment (HTA) reports play a significant role in managing policies and strategies to implement new health technologies. The organizational domain, however, is often under-represented in HTA reports. This study explored how organizational assessment is carried out in HTA reports and designed a new perspective through an empirical approach after the comparison with EUnetHTA's Core Model 3.0. METHODS: Full HTA reports were extracted from the websites of members of International Network of Agencies for HTA and the aspects relating to the organizational assessment were analysed. HTA reports were classified into 4 typologies of technologies (device, diagnosis/screening, intervention and organizational procedures) and organizational aspects described were explored through a framework of 5 domains and 15 subdomains from Core Model. Specific Multiple Correspondence Analyses were carried out to identify technology-related domains for organizational assessment in reports. RESULTS: The analysis showed that domains and subdomains of Core Model were not covered homogeneously by the organizational assessments in the HTA reports. Through Multiple Correspondence Analyses, four new technology-related dimensions were identified and named according to the Core Model's subdomains in the four new clusters. CONCLUSIONS: This study analyzed the significance of organizational assessments in current literature and the challenges of improving this domain in HTA reports. Through an empirical analysis, we proposed a new methodology to cover the most relevant aspects of organizational appraisal according to new domains to promote support to the assessment of organizational issues in reports and fulfil the needs of future HTA research.

[Accurate compiling of the hospital discharge records according to clinicians' perception: critical issues and perspectives]. / L'accurata compilazione delle schede di dimissione ospedaliera secondo la percezione dei medici: criticità e prospettive.

OBJECTIVES: to explore clinicians vision on hospital discharge records in order to identify useful elements to foster a more accurate compiling. DESIGN: qualitative research with phenomenological approach. SETTING AND PARTICIPANTS: participants were selected through purposive sampling among clinicians of two hospitals located in Sardinia; the sample included 76 people (32 medical directors and 44 doctors in training). MAIN OUTCOME MEASURES: identified codes for themes under investigation: vision of accurate compiling, difficulties, and proposals. RESULTS: collected data highlighted two prevailing visions, respectively focused on the importance of an accurate compiling and on the burden of such activity. The accurate compiling is hindered by the lack of motivation and training, by the limits of the registration system and the information technology, by the distortions induced by the prominent role of the hospital discharge records in the evaluation processes. Training, timely updating of the information system accompanied by a proper cross-cultural validation process, improvement of the computer system, and activation of support services could promote more accurate compiling. CONCLUSIONS: the implementation of services, unconnected with evaluation and control processes, dedicated to training and support in the compiling of the hospital discharge records and in the conduction of related epidemiological studies would facilitate the compliance to the compilation. Such services will make tangible the benefits obtainable from this registration system, increasing skills, motivation, ownership, and facilitating greater accuracy in compiling.

Are E-test and Vitek2 good choices for tigecycline susceptibility testing when comparing broth microdilution for MDR and XDR Acinetobacter baumannii?

This study reports the results of antimicrobial susceptibility testing of 10 MDR and 74 XDR Acinetobacter bauman- nii clinical isolates from our hospital routine. We used three different methods: two automated systems (Sensititre and VITEK 2) and one standardized manual method (E-test). Since many published papers refer to in vitro tests performed by E-test, the aim of this study was to test if this method is reliable for testing tigecycline. The results obtained show that E-test significantly overestimates the MIC of the broth microdilution (reference test), thus ob- taining a significant number of major errors (resistant instead of sensitive). VITEK 2 also shows the same problem, but it is less critical. We therefore conclude that these methods do not seem to be very reliable in the performance of susceptibility testing of MDR and XDR Acinetobacter baumannii against tigecycline.

Boardgames as an innovative approach to promote life skills and well-being among inmates: A scoping review protocol.

Over the past few decades, a growing body of evidence has emerged regarding the positive impact of boardgames in promoting life skills and well-being in various settings including health, education, and military schooling. However, the use of boardgames with inmates for cultural and educational purposes is still an unexplored and fragmented area of research. Incorporating boardgames into correctional settings can be a complex challenge for correctional stakeholders who seek to identify innovative tools to enhance inmate education and promote integration into society after incarceration. This article outlines our scoping review protocol designed to map and evaluate published and grey literature on the motivational, psychological, and pedagogical considerations involved in the design and use of boardgames as an innovative approach to promoting life skills and well-being among inmates.

Objective Non-Invasive Bio-Parametric Evaluation of Regenerated Skin: A Comparison of Two Acellular Dermal Substitutes.

Several dermal substitutes are available on the market, but there is no precise indication that helps surgeons choose the proper one. Few studies have tried to compare different xenogeneic bioengineered products, but no objective bio-parametric comparison has been made yet. Fifteen patients who underwent skin reconstruction with Integra® or Pelnac® were retrospectively evaluated. After at least 12 months of follow-up, an objective and quantitative assessment of several skin biophysical properties, such as color, texture, elasticity, hydration, glossiness and trans-epidermal water loss, were measured with non-invasive skin measurement devices. The grafted skin showed a reduction of the superficial hydration level and a tendency to lower values of trans-epidermal water loss with both dermal substitutes. Melanic and hemoglobin pigmentation were higher in comparison to the donor site in both groups, while a melanic pigmentation increase versus the surrounding skin was seen just with Integra®. Finally, the skin was found to be more elastic when reconstructed with Integra®. The skin barrier appeared to be intact in both groups. Hence, these substitutes are valuable means of skin regeneration. Integra® seems to be more advantageous for reconstructing areas that need more skin flexibility.

Candida auris as an Emergent Public Health Problem: A Current Update on European Outbreaks and Cases.

Candida auris is considered to be an emerging fungal pathogen and is related to high mortality rates, persistent candidemia, inconsistencies in susceptibility testing results and misidentification by available commercial identification systems. Multidrug-resistant (MDR) and pandrug-resistant (PDR) strains are increasingly detected. In Europe, hospital outbreaks caused by C. auris have been reported in the United Kingdom (UK), Italy and Spain; however, several cases have been sporadically detected in all European countries. C. auris is difficult to control despite enhanced control measures due to its ability to survive for a long time in environments and colonize patients for prolonged periods. An adequate laboratory diagnostic capacity and national surveillance are fundamental to rapidly detect new C. auris cases and to apply the correct measures to circumscribe them and prevent their spread. Our narrative review aims to highlight the primary C. auris outbreaks and case reports that have occurred in Europe.

Comparison of different methods for determining beta-lactam susceptibility in Pseudomonas aeruginosa.

This study compared the results of antimicrobial susceptibility testing of 77 clinical strains isolated for Pseudomonas aeruginosa to five beta-lactam agents: aztreonam, ceftazidime, imipenem, meropenem and piperacillin+tazobactam. Four different methods were employed: two automated systems (VITEK 2 and Sensititre) and two standardized manual methods (Kirby-Bauer and E-test). The concordances for the susceptibility categories were better for Kirby-Bauer (medium value =89.6%), followed by Sensititre (medium value =87.0%) and VITEK 2 (medium value =82.8%). The disk diffusion method did not present very major errors in comparison to the two automated systems.

Treatment with cefiderocol in K. pneumoniae KPC nosocomial external ventricular drainage meningitis: A brief report.

We report the case of successful use of cefiderocol (FDC) in a Carbapenemase Producing K. pneumoniae (CPKP) post-surgical meningitis in a 44-year-old man treated with antimicrobial therapy and external ventricular drainage (EVD). The patient was known for being colonised by CPKP; for this reason, therapy with ceftazidime/avibactam (CZA) plus fosfomycin and linezolid was started. After an initial response a CZA resistant CPKP strain was isolated from CSF culture, so the antibiotic therapy was modified to FDC with trimethoprim/sulfamethoxazole for 14 days, and EVD was replaced. A complete recovery was obtained. This is the first case report describing FDC administration in CPKP meningitis.

The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

Sex-Biased Expression of Pharmacogenes across Human Tissues.

Individual response to drugs is highly variable and largely influenced by genetic variants and gene-expression profiles. In addition, it has been shown that response to drugs is strongly sex-dependent, both in terms of efficacy and toxicity. To expand current knowledge on sex differences in the expression of genes relevant for drug response, we generated a catalogue of differentially expressed human transcripts encoded by 289 genes in 41 human tissues from 838 adult individuals of the Genotype-Tissue Expression project (GTEx, v8 release) and focused our analysis on relevant transcripts implicated in drug response. We detected significant sex-differentiated expression of 99 transcripts encoded by 59 genes in the tissues most relevant for human pharmacology (liver, lung, kidney, small intestine terminal ileum, skin not sun-exposed, and whole blood). Among them, as expected, we confirmed significant differences in the expression of transcripts encoded by the cytochromes in the liver, CYP2B6, CYP3A7, CYP3A5, and CYP1A1. Our systematic investigation on differences between male and female in the expression of drug response-related genes, reinforce the need to overcome the sex bias of clinical trials.

The Inhibitory Role of miR-486-5p on CSC Phenotype Has Diagnostic and Prognostic Potential in Colorectal Cancer.

Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second cause of cancer deaths. Increasing evidences supports the idea that the poor prognosis of patients is related to the presence of cancer stem cells (CSCs), a cell population able to drive cancer recurrence and metastasis. The deregulation of microRNAs (miRNAs) plays a role in the formation of CSC. We investigated the role of hsa-miR-486-5p (miR-486-5p) in CRC, CSCs, and metastasis, in order to reach a better understanding of the biomolecular and epigenetic mechanisms mir-486-5p-related. The expression of miR-486-5p was investigated in three different matrices from CRC patients and controls and in CSCs obtained from the CRC cell lines HCT-116, HT-29, and T-84. In the human study, miR-486-5p was up-regulated in serum and stool of CRC patients in comparison with healthy controls but down-regulated in tumor tissue when compared with normal mucosa. miR-486-5p was also down-regulated in the sera of metastatic patients. In vitro, miR-486-5p was down-regulated in CSC models and it induced an inhibitory effect on stem factors and oncogenes in the main pathways of CSCs. Our results provide a step forward in understanding the role of mir-486-5p in CRC and CSC, and suggest that further studies are needed to investigate its diagnostic and prognostic power, possibly in combination with other biomarkers.

131I SPECT/CT in the follow-up of differentiated thyroid carcinoma: incremental value versus planar imaging.

UNLABELLED: Planar 131I scintigraphy is routinely used to detect radioiodine-avid metastases of differentiated thyroid carcinoma (DTC). However, the modality has limitations, such as low sensitivity and lack of anatomic landmarks. We investigated whether SPECT with integrated low-dose CT may have additional value over planar imaging in detecting residue and metastases in DTC patients. METHODS: We studied 117 consecutive thyroidectomized DTC patients. On 2 different hybrid dual-head gamma-cameras (55 patients on one camera and 62 on the other), 108 patients underwent 131I diagnostic imaging and SPECT/CT, and 9 underwent posttherapeutic 131I planar imaging and SPECT/CT. We assigned an incremental value to SPECT/CT when it provided better identification and interpretation of the foci of radioiodine uptake, more correct anatomic localization and characterization, and precise differentiation between tumor lesions and physiologic uptake. RESULTS: Planar imaging showed 116 foci of uptake in 52 of 117 patients, and SPECT/CT showed 158 foci in 59 of 117 patients, confirming all foci seen on planar imaging but identifying an additional 28 occult foci in 10 of 52 patients. Fourteen occult foci were shown on SPECT/CT in 7 further patients whose planar imaging findings were negative. SPECT/CT correctly characterized 48 foci unclear on planar imaging, also defining location and extent. SPECT/CT was a determinant in classifying as neoplastic those foci for which planar imaging seemed to exclude malignancy, discriminating between residue and lymph node metastases in the neck, some of which were adjacent to salivary glands and had been missed on planar imaging. SPECT/CT also showed occult lesions in the mediastinum, abdomen, and pelvis and identified small bone metastases unsuspected on planar imaging. Globally, SPECT/CT had an incremental value over planar imaging in 67.8% of patients, modified therapeutic management in 35.6% of positive cases, and avoided unnecessary treatment in 20.3% of patients with only single benign lesions or physiologic uptake. CONCLUSION: 131I SPECT/CT improved planar data interpretation, showing a higher number of DTC lesions, more precisely localizing and characterizing DTC foci, and more correctly differentiating between physiologic uptake and metastases, thus permitting the most appropriate therapeutic approach to be chosen. A wider use of this method is suggested complementary to planar imaging in selected DTC patients.

99mTc-tetrofosmin SPECT in solitary pulmonary nodule evaluation.

A correct differential diagnosis between benign and malignant lesions is mandatory in patients with solitary pulmonary nodule (SPN). The aim of the present study was to investigate whether 99mTc-tetrofosmin SPECT may play a role in SPN evaluation. A consecutive series of 111 patients with an uncalcified

Pathogenic enteric Escherichia coli in children with and without diarrhea in Maputo, Mozambique.

A study was conducted on the circulation of potentially diarrheagenic Escherichia coli in two groups of children, both under the age of seven. The first group (548 children) suffered from mild diarrhea and attended the Xipamanine Health Center of Maputo, in Mozambique. The second group (380 children) included randomly chosen, asymptomatic, children from the same population. A total of 503 E. coli strains were isolated from the two groups of children (n=375 and 128, respectively). All E. coli strains were genotypically and phenotypically screened. The presence of virulence-associated genes was assessed by a set of multiplex PCR specific for st and lt genes of enterotoxic Escherichia coli (ETEC), eae and bfpA genes of enteropathogenic E. coli (EPEC), stx(1) and stx(2) of enterohemorrhagic E. coli (EHEC), ial of enteroinvasive E. coli (EIEC) and the species-specific gene uidA. Adhesion and citotoxicity of isolated E. coli were evaluated in vitro on different cell cultures. A total of 37 isolates harbored virulence-associated genes: 18 were classified as ETEC, (15 from symptomatic, and three from asymptomatic children), 16 as EPEC (respectively, 13 and 3) and three EIEC in the symptomatic group. No stx(1) or stx(2) genes, associated with enterohemorrhagic E. coli were found. On the basis of the adhesion pattern on HeLa cells, 167 E. coli were classified as diffusely adhering, (125 in patients and 42 in controls) and 67 as enteroaggregative, (50 and 17, respectively). To the best of our knowledge, this is the first report in the literature on the circulation of potentially diarrheagenic E. coli in Mozambique.

Mediastinal lymph node involvement in non-small cell lung cancer: evaluation with 99mTc-tetrofosmin SPECT and comparison with CT.

UNLABELLED: In patients with non-small cell lung cancer (NSCLC), surgical resection offers the best chance of cure. The preoperative assessment of mediastinal lymph node involvement is crucial to selecting those patients for whom surgery is indicated. METHODS: To evaluate the possible clinical role of (99m)Tc-tetrofosmin scintigraphy in the presurgical detection of mediastinal node metastases from NSCLC, we performed a prospective comparative study with CT on 83 patients (48 men, 35 women; age range, 38-81 y) with primary NSCLC (36 adenocarcinomas, 39 epidermoid squamous cell carcinomas, and 8 large cell anaplastic carcinomas). They underwent chest SPECT 20 min after (99m)Tc-tetrofosmin injection (740 MBq intravenously). The metastatic involvement of mediastinal nodes was assessed by histologic examination after mediastinoscopy or thoracotomy. Both chest CT and (99m)Tc-tetrofosmin scintigraphy were performed within 2 wk before the surgical staging. RESULTS: Metastatic mediastinal lymph nodes were found in 35 patients. (99m)Tc-Tetrofosmin imaging in assessing the mediastinal involvement yielded a sensitivity of 85.7%, a specificity of 89.6%, and an accuracy of 88.0%; CT results were 68.6%, 75.0%, and 72.3%, respectively. SPECT accuracy was significantly higher than CT accuracy (P < 0.05). However, precise anatomic localization of (99m)Tc-tetrofosmin uptake in the mediastinum was not always present on SPECT images. (99m)Tc-Tetrofosmin SPECT precisely detected the presence or absence of lymph node metastases in 33 of the 36 patients with positive CT findings (enlarged mediastinal nodes with a short axis > or =1 cm), with an accuracy (91.7%) significantly higher (P < 0.05) than that of CT (66.7%). CONCLUSION: (99m)Tc-Tetrofosmin SPECT is a useful presurgical noninvasive method to assess mediastinal lymph node involvement in NSCLC. In particular, it could play a clinical role in reducing the number of invasive staging surgical procedures in selected patients, especially in those with enlarged lymph nodes at CT. Fusing SPECT with CT images could further improve the interpretation of the scintigraphic data.

The usefulness of 99mTc-tetrofosmin SPECT in the detection of intrathoracic malignant lesions.

To evaluate the usefulness of 99mTc-tetrofosmin (TF) SPECT in the detection of intrathoracic malignant lesions, we studied 304 patients, 261 with malignant and 43 with benign lesions; 196 of the former had non-treated primary tumors, 193 lung cancer (LC) and 3 mesotheliomas, 11 had LC recurrences and 54 had metastases from different kinds of tumors. Twenty-nine patients with primary tumors were re-checked after chemotherapy or surgery. In all patients, after 740 MBq TF injection, both planar and SPECT images were acquired and analysed qualitatively, SPECT images also semiquantitatively. Scintigraphy was always compared to CT. SPECT showed higher sensitivity, specificity and accuracy values than CT (98.1, 90.7 and 97 vs. 96.2, 81.4, and 93.9%, respectively), their combined use achieving 100% sensitivity and 98.8% accuracy. Planar did not give more information than SPECT, showing a significantly lower sensitivity (63.2%) and accuracy (67.4%). SPECT showed higher accuracy values than CT and planar (86.9 vs. 78.3 and 69.6%) in NSCLC mediastinal lymph node staging. Moreover, SPECT was concordant with CT in correctly evaluating the response to chemotherapy or surgery in all monitorized primary tumors cases, except in one in whom only SPECT detected residual tumor. The semiquantitative analysis added useful information in differentiating malignant from benign lesions and in monitoring the response to chemo-therapy. TF SPECT appears a highly accurate diagnostic method in the detection of intrathoracic malignant lesions, in lungs and pleura, as well as in NSCLC mediastinal lymph node staging and in monitoring treatment effectiveness, playing a complementary role to CT in selected cases.

The usefulness of 99mTc-tetrofosmin SPECT scintimammography in the detection of small size primary breast carcinomas.

The aim of this study was to evaluate the usefulness of supine 99mTc-tetrofosmin SPECT in the detection of small size breast carcinomas (BC), for which planar scintimammography has showed a low sensitivity. We studied 93 patients with breast lesions

Epidemiology of bacterial resistance in gastro-intestinal pathogens in a tropical area.

During 1999-2000 a total of 4131 faecal specimens were collected and analysed at the medical centre St. Camille at Ouagadougou. Eight hundred and twenty-six (8.0%) grew significant bacteria. Escherichia coli (35%), Salmonella spp. (15%) and Shigella spp. (10%) were most frequently isolated. A large number of E. coli strains were resistant to aminopenicillins (>90%) and cotrimoxazole (80%); for Yersinia spp the resistance was 80 and 25%, respectively. Norfloxacin was the most active antibiotic but was rarely used. The study showed that it is necessary to create antibiotic-resistance surveillance centres in developing countries so that therapy may be appropriate and the spread of antibiotic resistance to other developed countries via increased emigration may be reduced.

[Study on in vitro susceptibility of Candida spp. isolated from blood culture]. / Studio sulla incidenza e sulla sensibilità in vitro di ceppi di Candida spp. isolati da sangue.

In recent years the incidence of bloodstream infections due to Candida species has progressively increased, partly due to the more critical conditions of hospitalized patients. There has been a significant increase in immune-compromised, diabetic and/or elderly patients, also with venous access, with a subsequent increase in Candida species isolated from bloodstream infections. In 2009-2010 in the hospitals of Mestre and Venice we isolated 123 Candida species from bloodstream infections: 59 Candida albicans, 28 Candida parapsilosis, 12 Candida glabrata, 9 Candida tropicalis, and 4 Geotrichum capitatum, while the 11 others belong to 8 different species. We calculated MIC for the following antifungal agents: fluconazole, itraconazole, voriconazole, 5-flucytosine, amphotericin B and caspofungin.